tbuckley/cabot-search huggingface dataset:
A self-guidance biological hybrid drug delivery system driven by anaerobes to inhibit the proliferation and metastasis of colon cancer
Authors: Huijuan Zhang, Yaping Wang, Mengting Li, Kexuan Cao, Zijun Qi, Ling Zhu, Zhenzhong Zhang, Lin Hou
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Colorectal cancer is often accompanied by multiple organ metastasis. Anaerobic Bifidobacterium Infantis (BI) bacterial can selectively grow in hypoxic colorectal tumor microenvironment (TME), to own the natural advantage of preferentially colorectal tumor targeting. Herein, a self-guidance biological hybrid drug delivery system (BI-ES-FeAlg/DOX) based on BI was constructed to inhibit the proliferation and metastasis of colon cancer. Results demonstrated that BI-ES-FeAlg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues. Then DOX was released to kill tumor cells along with the phase transition (solid to liquid) of FeAlg hydrogel, due to Fe3+ was reduced to Fe2+by intracellular GSH. Meanwhile, BI-ES selectively colonized into tumors and expressed endostatin (ES) protein to down-regulate VEGF and bFGF expression, exerting anti-angiogenic effect. Moreover, FeAlg catalyzed H2O2 in the local tumor to generate cytotoxic ·OH, further enhancing the antitumor effect. The pharmacodynamic result in AOM/DSS model proved that BI-ES-FeAlg/DOX had the best therapeutic effect, with the final V/V0 of 2.19 ± 0.57, which was significantly lower than the other groups. Meanwhile, on CT-26 tumor-bearing model, it also showed an outstanding anti-tumor effect with inhibition rate of 82.12% ± 3.08%. In addition, lung metastases decreased significantly in tumor metastasis model after BI-ES-FeAlg/DOX treatment.
Nuclear transport of STAT6 determines the matrix rigidity dependent M2 activation of macrophages
Authors: Jeong-Ki Kim, Seong-Beom Han, Serk In Park, In-San Kim, Dong-Hwee Kim
Journal: Biomaterials (2022)

Alternatively activated or M2 macrophages, as opposed to the well characterized pro-inflammatory or M1 macrophages, vitally regulate anti-inflammation, wound healing, and tissue repair to maintain tissue homeostasis. Although ubiquitous presence of macrophages in diverse tissues, exposed to different physical environments, infers distinct immune responses of M2 macrophages with high phenotypic heterogeneity, the underlying mechanism of how the varying extracellular mechanical conditions alter their immunological activation remains unclear. Here, we demonstrate that M2 activation requires a threshold mechanical cue from the extracellular microenvironment, and matrix rigidity-dependent macrophage spreading is mediated by the F-actin formation that is essential to regulate mechanosensitive M2 activation of macrophages. We identified a new mechanosensing function of STAT6 (signal transducer and activator of transcription 6), a key transcription factor for M2 activation, whose intranuclear transportation is promoted by the rigid matrix that facilitates the F-actin formation. Our findings further highlight the critical role of mechanosensitive M2 activation of macrophages in long-term adaptation to the extracellular microenvironment by bridging nuclear mechanosensation and immune responses.
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Authors: Patricia Morrissey, Christine Burgos-Clavel
Journal: Kidney International (2022)

Kidney International is devoted to kidney research.It aims to inform the researcher, the clinical investigator, and the practicing nephrologist on all aspects of kidney research.These include the latest clinical studies on emerging developments in nephrology and the highest level of original research studies in clinical and basic kidney research.The journal reflects the field through critical reviews, commentaries, original articles, remarkable images, news features, guidelines, and problem-focused articles for the diagnosis and treatment of kidney patients.
Table of Contents
Authors: Yun Xia, P Coates, Masaomi Nangaku, Zhi Yu, Matthias Wuttke, Ewout Hoorn, Jeroen De Baaij, Matthias Barton, Stuart Shankland, Oliver Wessely, Anna Francis, Muhammad Iqbal, Abdul Hafidz, Udeme Ekrikpo, Titi Chen, Eranga Wijewickrama, Elliot Tannor, Georges Nakhoul, Michelle Wong, Nikhil Pereira-Kamath, Rahul Chanchlani, Robert Kalyesubula, Sabine Karam, Vivek Kumar, Viviane Calice-Silva, Vivekanand Jha, Ian De Boer, Kamlesh Khunti, Tami Sadusky, Katherine Tuttle, Joshua Neumiller, Connie Rhee, Sylvia Rosas, Peter Rossing, George Bakris
Journal: Kidney International (2022)
Tumor-induced osteomalacia
Authors: Anand K. Annamalai, Ajit Shinto, Subramanian Aram, Veeranathevar Ananji Prabhu, Radhakrishnan Santhi, Chandrasekaran Gopalakrishnan, Mathirajan Chelian, Kaliappan Gurusamy Srinivasan
Journal: Kidney International (2022)
Executive summary of the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease: an update based on rapidly emerging new evidence
Authors: Peter Rossing, M. Luiza Caramori, Juliana C.N. Chan, Hiddo J.L. Heerspink, Clint Hurst, Kamlesh Khunti, Adrian Liew, Erin D. Michos, Sankar D. Navaneethan, Wasiu A. Olowu, Tami Sadusky, Nikhil Tandon, Katherine R. Tuttle, Christoph Wanner, Katy G. Wilkens, Sophia Zoungas, Jonathan C. Craig, David J. Tunnicliffe, Marcello A. Tonelli, Michael Cheung, Amy Earley, Ian H. de Boer
Journal: Kidney International (2022)

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating people with diabetes and CKD. Topic areas for which recommendations are updated based on new evidence include Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. The content of previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) has been deemed current and was not changed. This guideline update was developed according to an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence, and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, and areas for which additional research is needed are presented.
KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease
Authors: Peter Rossing, M. Luiza Caramori, Juliana C.N. Chan, Hiddo J.L. Heerspink, Clint Hurst, Kamlesh Khunti, Adrian Liew, Erin D. Michos, Sankar D. Navaneethan, Wasiu A. Olowu, Tami Sadusky, Nikhil Tandon, Katherine R. Tuttle, Christoph Wanner, Katy G. Wilkens, Sophia Zoungas, Ian H. de Boer
Journal: Kidney International (2022)

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating diabetes and CKD. Topic areas for which recommendations are updated include: Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. Previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) have been deemed current and their content has remained unchanged. Development of this guideline update followed an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the “Grading of Recommendations Assessment, Development and Evaluation” (GRADE) approach. Limitations of the evidence are discussed and areas of future research are also presented.
John Launer: When outpatient appointments are put on hold
Authors: John Launer
Journal: BMJ (2022)

I have a long term medical condition that requires regular hospital review.In theory this should happen every six months.Nowadays, most of the appointment letters or texts I receive from the hospital tell me that my next review has been postponed, usually for a further six months.A series of such delays, beginning before the covid-19 pandemic but extending into it, led at one point to a gap of nearly three years without a face-to-face or phone appointment.Because I'm a doctor and my condition is fairly stable, I can more or less cope with the resulting anxiety.I can access my GP fairly easily when I need to, and not only because I'm a colleague.I also know from the inside how much pressure the NHS is under and how threadbare its fabric has become: it was bad before the pandemic and is dangerously so now.
How the US scrapp­­­­ing of Roe <i>v</i> Wade threatens the global medical abortion revolution
Authors: Sally Howard, Geetanjali Krishna
Journal: BMJ (2022)

Medical abortions are a global success story, and not one that will be easily derailed by the legislative backsliding in the US. Time, now, to close the access gaps, report <b>Sally Howard and Geetanjali Krishna</b>
Wearable Hydrogel‐Based Epidermal Sensor with Thermal Compatibility and Long Term Stability for Smart Colorimetric Multi‐Signals Monitoring
Authors: Fei Han, Xueyong Xie, Tiansong Wang, Chaoyu Cao, Juju Li, Tianying Sun, Hao Liu, Songmei Geng, Zhao Wei, Jing Li, Feng Xu
Journal: Advanced Healthcare Materials (2022)

Hydrogel-based wearable epidermal sensors (HWESs) have attracted widespread attention in health monitoring, especially considering their colorimetric readout capability. However, it remains challenging for HWESs to work at extreme temperatures with long term stability due to the existence of water. Herein, a wearable transparent epidermal sensor with thermal compatibility and long term stability for smart colorimetric multi-signals monitoring is developed, based on an anti-freezing and anti-drying hydrogel with high transparency (over 90% transmittance), high stretchability (up to 1500%) and desirable adhesiveness to various kinds of substrates. The hydrogel consists of polyacrylic acid, polyacrylamide, and tannic acid-coated cellulose nanocrystals in glycerin/water binary solvents. When glycerin readily forms strong hydrogen bonds with water, the hydrogel exhibits outstanding thermal compatibility. Furthermore, the hydrogel maintains excellent adhesion, stretchability, and transparency after long term storage (45 days) or at subzero temperatures (-20 °C). For smart colorimetric multi-signals monitoring, the freestanding smart colorimetric HWESs are utilized for simultaneously monitoring the pH, T and light, where colorimetric signals can be read and stored by artificial intelligence strategies in a real time manner. In summary, the developed wearable transparent epidermal sensor holds great potential for monitoring multi-signals with visible readouts in long term health monitoring.
Explainable medical imaging AI needs human-centered design: guidelines and evidence from a systematic review
Authors: Haomin Chen, Catalina Gomez, Chien-Ming Huang, Mathias Unberath
Journal: npj Digital Medicine (2022)

Abstract Transparency in Machine Learning (ML), often also referred to as interpretability or explainability, attempts to reveal the working mechanisms of complex models. From a human-centered design perspective, transparency is not a property of the ML model but an affordance, i.e., a relationship between algorithm and users. Thus, prototyping and user evaluations are critical to attaining solutions that afford transparency. Following human-centered design principles in highly specialized and high stakes domains, such as medical image analysis, is challenging due to the limited access to end users and the knowledge imbalance between those users and ML designers. To investigate the state of transparent ML in medical image analysis, we conducted a systematic review of the literature from 2012 to 2021 in PubMed, EMBASE, and Compendex databases. We identified 2508 records and 68 articles met the inclusion criteria. Current techniques in transparent ML are dominated by computational feasibility and barely consider end users, e.g. clinical stakeholders. Despite the different roles and knowledge of ML developers and end users, no study reported formative user research to inform the design and development of transparent ML models. Only a few studies validated transparency claims through empirical user evaluations. These shortcomings put contemporary research on transparent ML at risk of being incomprehensible to users, and thus, clinically irrelevant. To alleviate these shortcomings in forthcoming research, we introduce the INTRPRT guideline , a design directive for transparent ML systems in medical image analysis. The INTRPRT guideline suggests human-centered design principles, recommending formative user research as the first step to understand user needs and domain requirements. Following these guidelines increases the likelihood that the algorithms afford transparency and enable stakeholders to capitalize on the benefits of transparent ML.
Defining digital surgery for the future
Authors: Marium M. Raza, Kaushik P. Venkatesh, James A. Diao, Joseph C. Kvedar
Journal: npj Digital Medicine (2022)

Abstract Innovations in robotics, virtual and augmented reality, and artificial intelligence are being rapidly adopted as tools of “digital surgery”. Despite its quickly emerging role, digital surgery is not well understood. A recent study defines the term itself, and then specifies ethical issues specific to the field. These include privacy and public trust, consent, and litigation.
A Dynamic rRNA Ribomethylome Drives Stemness in Acute Myeloid Leukemia
Authors: Fengbiao Zhou, Nesrine Aroua, Yi Liu, Christian Rohde, Jingdong Cheng, Anna-Katharina Wirth, Daria Fijalkowska, Stefanie Göllner, Michelle Lotze, Haiyang Yun, Xiaobing Yu, Caroline Pabst, Tim Sauer, Thomas Oellerich, Hubert Serve, Christoph Röllig, Martin Bornhäuser, Christian Thiede, Claudia Baldus, Michaela Frye, Simon Raffel, Jeroen Krijgsveld, Irmela Jeremias, Roland Beckmann, Andreas Trumpp, Carsten Müller-Tidow
Journal: Cancer Discovery (2022)

The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, and functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity in vivo. A comprehensive analysis of the rRNA 2'-O-methylation landscape of 94 patients with acute myeloid leukemia (AML) revealed dynamic 2'-O-methylation specifically at exterior sites of ribosomes. The rRNA 2'-O-methylation pattern is closely associated with AML development stage and LSC gene expression signature. Forced expression of the 2'-O-methyltransferase fibrillarin (FBL) induced an AML stem cell phenotype and enabled engraftment of non-LSC leukemia cells in NSG mice. Enhanced 2'-O-methylation redirected the ribosome translation program toward amino acid transporter mRNAs enriched in optimal codons and subsequently increased intracellular amino acid levels. Methylation at the single site 18S-guanosine 1447 was instrumental for LSC activity. Collectively, our work demonstrates that dynamic 2'-O-methylation at specific sites on rRNAs shifts translational preferences and controls AML LSC self-renewal. We establish the complete rRNA 2'-O-methylation landscape in human AML. Plasticity of rRNA 2'-O-methylation shifts protein translation toward an LSC phenotype. This dynamic process constitutes a novel concept of how cancers reprogram cell fate and function. This article is highlighted in the In This Issue feature, p. 247.
Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Shruthy Suresh, Roy Rabbie, Manik Garg, Dianne Lumaquin, Ting-Hsiang Huang, Emily Montal, Yilun Ma, Nelly M Cruz, Xinran Tang, Jérémie Nsengimana, Julia Newton-Bishop, Miranda V. Hunter, Yuxin Zhu, Kevin Chen, Elisa de Stanchina, David J. Adams, Richard M. White
Journal: Cancer Discovery (2022)

Abstract In melanoma, predicting which tumors will ultimately metastasize guides treatment decisions. Transcriptional signatures of primary tumors have been utilized to predict metastasis, but which among these are driver or passenger events remains unclear. We used data from the adjuvant AVAST-M trial to identify a predictive gene signature in localized tumors that ultimately metastasized. Using a zebrafish model of primary melanoma, we interrogated the top genes from the AVAST-M signature in vivo. This identified GRAMD1B, a cholesterol transfer protein, as a bona fide metastasis suppressor, with a majority of knockout animals rapidly developing metastasis. Mechanistically, excess free cholesterol or its metabolite 27-hydroxycholesterol promotes invasiveness via activation of an AP-1 program, which is associated with increased metastasis in humans. Our data demonstrate that the transcriptional seeds of metastasis are embedded within localized tumors, suggesting that early targeting of these programs can be used to prevent metastatic relapse. Significance: We analyzed human melanoma transcriptomics data to identify a gene signature predictive of metastasis. To rapidly test clinical signatures, we built a genetic metastasis platform in adult zebrafish and identified GRAMD1B as a suppressor of melanoma metastasis. GRAMD1B-associated cholesterol overload activates an AP-1 program to promote melanoma invasion. This article is highlighted in the In This Issue feature, p. 1
Learning to distinguish progressive and non-progressive ductal carcinoma in situ
Authors: Anna K. Casasent, Mathilde M. Almekinders, Charlotta Mulder, Proteeti Bhattacharjee, Deborah Collyar, Alastair M. Thompson, Jos Jonkers, Esther H. Lips, Jacco van Rheenen, E. Shelley Hwang, Serena Nik-Zainal, Nicholas E. Navin, Jelle Wesseling, Elinor J. Sawyer, Helen R. Davies, Andrew Futreal, Nicholas E. Navin, E. Shelley Hwang, Jacco van Rheenen, Fariba Behbod, Marjanka Schmidt, Lodewyk F. A. Wessels, Daniel Rea, Hilary Stobart, Donna Pinto, Ellen Verschuur, Marja van Oirsouw
Journal: Nature reviews. Cancer (2022)
Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety
Authors: Nicholas A. Vitanza, Ashley L. Wilson, Wenjun Huang, Kristy Seidel, Christopher Brown, Joshua A. Gustafson, Jason K. Yokoyama, Adam J. Johnson, Blake A. Baxter, Ryan W. Koning, Aquene N. Reid, Michael Meechan, Matthew C. Biery, Carrie Myers, Stephanie D. Rawlings-Rhea, Catherine M. Albert, Samuel R. Browd, Jason S. Hauptman, Amy Lee, Jeffrey G. Ojemann, Michael E. Berens, Matthew D. Dun, Jessica B. Foster, Erin E. Crotty, Sarah E.S. Leary, Bonnie L. Cole, Francisco A. Perez, Jason N. Wright, Rimas J. Orentas, Tony Chour, Evan W. Newell, Jeffrey R. Whiteaker, Lei Zhao, Amanda G. Paulovich, Navin Pinto, Juliane Gust, Rebecca A. Gardner, Michael C. Jensen, Julie R. Park
Journal: Cancer Discovery (2022)

Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3-specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), a first-in-human phase I trial administering repeated locoregional B7-H3 CAR T cells to children with recurrent/refractory CNS tumors and DIPG. Here, we report the results of the first three evaluable patients with DIPG (including two who enrolled after progression), who received 40 infusions with no dose-limiting toxicities. One patient had sustained clinical and radiographic improvement through 12 months on study. Patients exhibited correlative evidence of local immune activation and persistent cerebrospinal fluid (CSF) B7-H3 CAR T cells. Targeted mass spectrometry of CSF biospecimens revealed modulation of B7-H3 and critical immune analytes (CD14, CD163, CSF-1, CXCL13, and VCAM-1). Our data suggest the feasibility of repeated intracranial B7-H3 CAR T-cell dosing and that intracranial delivery may induce local immune activation. This is the first report of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG and includes preliminary tolerability, the detection of CAR T cells in the CSF, CSF cytokine elevations supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF. This article is highlighted in the In This Issue feature, p. 1.
The diagnosis, classification, and treatment of sarcoma in this era of artificial intelligence and immunotherapy
Authors: Amandine Crombé, Mathtieu Roulleau‐Dugage, Antoine Italiano
Journal: Cancer Communications (2022)

Abstract Soft‐tissue sarcomas (STS) represent a group of rare and heterogeneous tumors associated with several challenges, including incorrect or late diagnosis, the lack of clinical expertise, and limited therapeutic options. Digital pathology and radiomics represent transformative technologies that appear promising for improving the accuracy of cancer diagnosis, characterization and monitoring. Herein, we review the potential role of the application of digital pathology and radiomics in managing patients with STS. We have particularly described the main results and the limits of the studies using radiomics to refine diagnosis or predict the outcome of patients with soft‐tissue sarcomas. We also discussed the current limitation of implementing radiomics in routine settings. Standard management approaches for STS have not improved since the early 1970s. Immunotherapy has revolutionized cancer treatment; nonetheless, immuno‐oncology agents have not yet been approved for patients with STS. However, several lines of evidence indicate that immunotherapy may represent an efficient therapeutic strategy for this group of diseases. Thus, we emphasized the remarkable potential of immunotherapy in sarcoma treatment by focusing on recent data regarding the immune landscape of these tumors. We have particularly emphasized the fact that the development of immunotherapy for sarcomas is not an aspect of histology (except for alveolar soft‐part sarcoma) but rather that of the tumor microenvironment. Future studies investigating immunotherapy strategies in sarcomas should incorporate at least the presence of tertiary lymphoid structures as a stratification factor in their design, besides including a strong translational program that will allow for a better understanding of the determinants involved in sensitivity and treatment resistance to immune‐oncology agents.
Association of hematologic response and assay sensitivity on the prognostic impact of measurable residual disease in acute myeloid leukemia: a systematic review and meta-analysis
Authors: Nicholas J. Short, Chenqi Fu, Donald A. Berry, Roland B. Walter, Sylvie D. Freeman, Christopher S. Hourigan, Xuelin Huang, Graciela Nogueras Gonzalez, Hyunsoo Hwang, Xinyue Qi, Hagop Kantarjian, Shouhao Zhou, Farhad Ravandi
Journal: Leukemia (2022)